Modification of the polar head group of acetyl glyceryl ether phosphorylation and subsequent effects upon platelet activation

A series of phosphoglycerides containing the same structural unit, 1-O-alkyl-2-acetyl-sn-glycerol, was prepared with the following polar head groups: -3-phosphoric acid (AGEPA), -3-phosphorylethanol (AGEPEt), -3-phosphorylethanolamine (AGEPE), -3-phosphoryl-N-monomethylethanolamine (AGEPMME), -3-phosphoryl-N,N-dimethylethanolamine (AGEPDME), and -3-phosphorylcholine (AGEPC). These compounds were synthesized primarily by phospholipase D modification of AGEPC. The characterization of these derivatives was achieved through thin layer chromatography, infrared spectrometry, gas-liquid chromatography, and combined gas-liquid chromatography-mass spectrometry. Their ability to induce irreversible aggregation and 50% secretion of serotonin from washed rabbit platelets was investigated. The latter secretory activity, expressed on a molar basis (60 s following platelet stimulation) was shown to be particularly sensitive to the nature of the polar head group as follows; AGEPA 8.3 x 10^-7 M; AGEPE, 6.8 x 10^-7 M; AGEPEt, 4.0 x 10^-7 M; AGEPMME, 3.7 x 10^-9 M; AGEPDME, 4.5 x 10^-10 M; and AGEPC, 1.8 x 10^-10 M. It was concluded that the polar head group of the various acetyl glyceryl ether phosphoglycerides had an important role in expressing the biological activity of this unique type of phosphoglyceride towards platelets. It appears likely that the recognition site (receptor site) on platelets is more reactive to the dimethylethanolamine or the quaternary ammonium base, choline, than to any of the other polar head groups under consideration.